State-dependent modulation of mSlo, a cloned calcium-dependent potassium channel.

The mouse slopoke calcium-dependent potassium channel (mSlo) has been expressed heterologously in COS cells, and incorporated from COS cell membranes into artificial phospholipid bilayers. Under control conditions, the channel is not modulated by ATP. However, when mSlo is treated first with the calcium-dependent potassium channel opener NS004, which itself increases the open probability of the channel, subsequent addition of ATP causes a large further increase in channel open probability. An increase in channel activity is not by itself sufficient to confer sensitivity to ATP, because ATP does not modulate channels whose open probability has been increased by elevated calcium or depolarized voltage. The ATP analog AMP-PNP has only minimal effects on channel activity after treatment with NS004, suggesting that hydrolysis of the ATP is required for its action on mSlo. A peptide inhibitor of the calcium/calmodulin-dependent protein kinase II (CaMKII) blocks the modulation of mSlo by ATP, whereas peptide inhibitors of other serine/threonine protein kinases are without effect. The results are consistent with a state-dependent modulation of mSlo by ATP, possibly via phosphorylation.